The Mount Sinai journal of medicine, New York
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Type 2 diabetes mellitus is a multifactorial metabolic disorder. It is characterized by chronic hyperglycemia, insulin resistance, and a relative insulin secretion defect. The prevalence of type 2 diabetes mellitus has risen worldwide in large part because of an increase in obesity and sedentary lifestyles. ⋯ The evolving understanding about the influence of the incretin effect, insulin signal transduction, adipose tissue, intra-islet cell communication, and inflammation is changing the way in which we view type 2 diabetes mellitus. This new understanding will eventually provide us with new treatment approaches to help patients who have type 2 diabetes mellitus. This article gives a review of the current and emerging concepts of the pathophysiology of type 2 diabetes mellitus.
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The incretins have emerged as key targets in the modern treatment of type 2 diabetes mellitus. Understanding the physiology of the incretins is essential to the physician's ability to appropriately use emerging pharmacotherapies that target this system. This review describes incretin physiology and discusses recent trials of drugs that modulate this system in the treatment of type 2 diabetes. ⋯ As the articles show, new medications manipulating the incretin system are an important part of treating type 2 diabetes. The cost of these drugs and their potential side effects in comparison with existing agents must be considered when they are being selected as part of a treatment regimen. However, the evidence to date offers much promise and enthusiasm.
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Cardiovascular disease is the predominant cause of death in diabetic patients, and reducing the risk of cardiovascular disease in diabetics has recently been the focus of several highly publicized large trials, including ACCORD (Action To Control Cardiovascular Risk in Diabetes), ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation), and VADT (Veterans Affairs Diabetes Trial). These studies randomized high-risk diabetic patients into either intensive treatment or standard treatment. The glycemic control arm of ACCORD was terminated 17 months before the planned end of the study because of a finding of significantly increased all-cause and cardiovascular mortality in the intensive treatment group. ⋯ None of these were validated in post hoc analyses of the trial data, and the cause of the increased mortality remains elusive. Subgroup analyses suggest that those who start off with better control of their diabetes or without preexisting cardiovascular disease may have the most to gain from tight glycemic control. Reducing the risk of macrovascular disease and death in diabetic patients requires not only attention to glucose control but also meticulous attention to control of nonglycemic risk factors, including hypertension, hyperlipidemia, smoking, lack of exercise, and unhealthy diet as well as timely prescription of medications with proven preventative benefits, such as aspirin and statins.
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Clinicians are faced with an expansive array of treatment choices when caring for patients with type 2 diabetes. Because patient compliance may be affected when media sensationalism about controversial findings is misunderstood, we sought to clarify the recent controversy surrounding the cardiovascular and bone-health risks of thiazolidinediones, the risk of lactic acidosis with metformin, and the risk of hypoglycemia with oral therapies. The side effect profile of thiazolidinediones includes fluid retention, heart failure; and an increased risk of fracture. ⋯ Patients on sulfonylureas and meglitinides have the highest incidence of hypoglycemia because of their pharmacological action of increasing insulin secretion. Of the sulfonylureas, glyburide presents the highest risk of hypoglycemia. Combination therapies, especially those regimens containing a sulfonylurea, increase the risk of hypoglycemia.